title: In vitro and in vivo antiproliferative effect of a combination of ultraviolet-A and alkoxy furocoumarins isolated from Umbelliferae medicinal plants, in melanoma cells.
abstract: We examined the effects of six furocoumarins with alkoxy groups at the C-5 or C-8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C-5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G2/M arrest at concentrations of 0.1-10.0 μm. Furthermore, three furocoumarins with an alkoxy group at C-8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G2/M at concentrations of 0.1-1.0 μm. UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10-bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg(-1) (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C-5 or C-8 were due to G2/M arrest of the cell cycle by an increase in phosphor-Chk1 and decrease in phospho-cdc2.
authors.affiliation: Division of Biochemical Pharmacology, Department of Basic Medical Research, Ehime University Graduate School of Medicine, Toon City, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Maho
authors.initials: M
authors.lastname: Sumiyoshi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kimiye
authors.initials: K
authors.lastname: Baba
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008812:Mice, Hairless; D010946:Plants, Medicinal / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D011564:Furocoumarins